Fibromyalgia (FM) is characterized by chronic pain, tenderness, and stiffness in skeletal muscle. FM afflicts 4 to 6 million people in the US, 80% of which are women. Chronic fatigue syndrome (CFS) is very similar to FM. About 75% of patients meeting the diagnostic criteria of CFS also meet the diagnostic criteria for FM. There is a linear increase in the prevalence of FM up to the eighth decade of life. Chronic pain in FM patients is not well managed in the clinic, severely affects their quality of life, and limits mobility and motor activities. We are proposing to establish a tissue bank to make brain and spinal cord tissue available to study FM. Further, we propose to use the collected spinal cord tissue to determine the extent to which chronic pain in FM patients is associated with glial activation and concomitant proinflammatory cytokine production. Glial activation is linked in animal models to pain facilitation. While studying rodent pain models has proven fruitful, there is a critical need to extend investigations from rodents to humans. Rodent studies predict that glial activation and glial proinflammatory products (e.g. tumor necrosis factor (TNF), interleukin-1 (IL-1) and IL-1B) will be key spinal mediators in human chronic pain. It is critical to test the extent that glia are involved in human pain regulation. It cannot be assumed based on animal data that glial activation and their proinflammatory cytokine products are associated with human chronic pain. Mechanisms of pain facilitation elucidated using animal models have at times proven disappointing when applied to human chronic pain. This is a critical problem because until this information becomes available, it will not be possible to develop drugs targeting glial activation or their inflammatory products for chronic pain treatment. The studies also will extend our knowledge of basic mechanisms in FM pain. The objectives of this application are 1) to increase enrollment of FM patients into the brain donation program at the Sun Health Research Institute (SHRI), collect relevant clinical data and to obtain blood, cerebrospinal fluid, spinal cords and brains from enrolled patients rapidly after death and 2) to determine the extent to which FM patients have glial activation or proinflammatory cytokine production in pain-processing areas of the brain and spinal cord using the tissue collected. These objectives will be fulfilled by completing the following Specific Aims: 1) we will actively recruit and enroll FM patients into the existing brain/spinal cord donation program at SHRI. 2) We will assess the extent to which there is immunohistochemical, mRNA or protein evidence of glial activation and proinflammatory cytokine production in spinal tissues of FM patients compared to age matched pain free controls. A research team that uniquely combines experts in pain research, FM, neurology, neuropsychology and personnel with extensive expertise with a neuroscience clinical research center and CMS tissue donation program have been assembled to complete these Aims. [unreadable] [unreadable] [unreadable]